chr1-52431054-G-A

Position:

• chr1-52431054-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009881.3(TUT4):​c.4670C>T​(p.Ala1557Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1557S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUT4 NM_001009881.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.00

Genes affected

TUT4 (HGNC:28981): (terminal uridylyl transferase 4) Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; negative regulation of transposition, RNA-mediated; and stem cell population maintenance. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleolus. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18178788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT4	NM_001009881.3	c.4670C>T	p.Ala1557Val	missense_variant	28/30	ENST00000257177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT4	ENST00000257177.9	c.4670C>T	p.Ala1557Val	missense_variant	28/30	1	NM_001009881.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718516

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2023

The c.4670C>T (p.A1557V) alteration is located in exon 28 (coding exon 27) of the ZCCHC11 gene. This alteration results from a C to T substitution at nucleotide position 4670, causing the alanine (A) at amino acid position 1557 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	.;L
MutationTaster	Benign	0.54	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.062
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.11	.;B
Vest4		0.11
MutPred		0.25		.;Gain of sheet (P = 0.0149);
MVP		0.12
MPC		0.37
ClinPred		0.69	D
GERP RS		5.4
Varity_R		0.12
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-52896726;